Method of controlling plant growth and 3-substituted lumazines used in such method

ABSTRACT

A METHOD FOR CONTROLLING PLANT GROWTH AND NEW COMPOUNDS USED IN SUCH METHOD. THE METHOD INCLUDES THE STEP OF APPLYING THE NEW COMPOUNDS TO THE LOCUS TO BE PROTECTED. THE COMPOUNDS ARE 3-SUBSTITUTED-LUMAZINES, WHERE THE 3-SUBSTITUENT IS A MEMBER OF THE GROUP CONSISTING OF ALKYL GROUPS HAVING FROM 2 TO 8 CARBON ATOMS AND CYCLOALKYL GROUPS HAVING FROM 3 TO 12 CARBON ATOMS.

United States Patent Office Patented May 8, 1973 US. Cl. 260251.5 5 Claims ABSTRACT OF THE DISCLOSURE A method for controlling plant growth and new compounds used in such method. The method includes the step of applying the new compounds to the locus to be protected. The compounds are 3-substituted-lumazines, where the S-substituent is a member of the group consisting of alkyl groups having from 2 to 8 carbon atoms and cycloalkyl groups having from 3 to 12 carbon atoms.

This is a continuation-in-part of application Ser. No.

740,045, now abandoned, and of application Ser. No.

740,099, now abandoned, both filed June 26, 1968.

BACKGROUND OF THE INVENTION This invention relates to a method for controlling plant growth, and to new compounds used in such method which have been found to have utility as plant growth regulators, selective weed killers, defoliating agents, and as agricultural chemicals.

In recent years increased crop yields have been made possible by the development and use of chemicals which are specifically toxic to weeds, yet do not damage crops around which they are applied. In general, the currently available chemicals which are most desired for their selectivity and as total herbicides are sufficiently expensive that expense is a significant factor in their use. Therefore, new compounds and inexpensive methods for producing such compounds are constantly being sought.

In addition, while many compounds presently on the market are effective to control the growth of certain species of weeds, they are ineffective against others. Thus new herbicides which have broad spectrum effectiveness against a Wide variety of weeds are continually being sought. A family of 3-substituted lumazines of the type described herein has been found particularly effective.

An object of the invention is to provide a method for controlling Weeds.

Another object of the invention is the provision of a new family of compounds useful as broad spectrum herbicides.

Other objects and advantages of this invention will be apparent from the description to follow:

SUMMARY OF THE INVENTION The compositions of the invention comprise compounds .of the type exemplified by the formula below.

Infrared and nuclear magnetic resonance spectra indlcate that the above formula represents the principal structure, but that a minor portion may be in the enolic Such compounds have been found to be active as selective herbicides when R has been selected from the group consisting of alkyl groups having from 2 to 8 carbon atoms and cycloalkyl groups having from 3 to 12 carbon atoms.

The method of the invention comprises applying an effective quantity of at least one of the above compounds to the locus to be protected.

The 3-substituted lumazines can be prepared by using 2,3-pyrazinedicarboximide 1 as a starting material, producing a diamide by reacting the imide with an amine of the formula RNH wherein R is selected from the group consisting of alkyl groups having from 2 to 8 carbon atoms and cycloalkyl groups having from 3 to 12 carbon atoms, and reacting the amide with sodium hypochlorite in the presence of sodium hydroxide. The preparation of N-isopropyl-2,3-pyrazinedicarboxamide is used as an example.

EXAMPLE 1 Preparation of N-isopropyl-2,3-pyrazinedicarboxamide A 250 ml., 3-necked flask equipped with a stirrer, thermometer and condenser fitted with a CaCl drying tube, was charged, at room temperature, with 26.1 g. of 2,3- pyrazinedicarboximide and 200 ml. of tetrahydrofuran. To the stirred reaction mixture was added, in one portion, 11.8 g. of isopropylamine. Within one hour, a clear brown solution was observed. After three hours, the solution was cooled to 2 2 whereupon solids formed. The solids were removed by filtration. The filtrate was concentrated to a volume of 10-15 ml. in vacuo and a second crop of solids removed by filtration. Both crops of solids were air dried under infrared lamps. The overall yield of material was 97.8 percent with a melting point of 182, and an elemental analysis as follows. Theory (percent): C, 51.92; H, 5.8l; N, 26.91. Found (percent): C, 51.82; H, 5.80; N, 27.06.

1 Gabriel and Sonn, Chem. Ber., 40, 4857. A11 temperatures reported herein and in the attached claims are in degrees centigrade unless otherwise specified.

3 the same manner with appropriate substitution being made in the selection of the amine, RNH R having the meaning previously designated.

The 3-substituted lumazines of the invention can be produced from the corresponding dicarboxamide by rewas 80", after 38 minutes of heating 89. The heating mantle was then removed, and the flask was immersed in an ice bath and cooled to 50. The reaction mixture was then filtered, and the filtrate was cooled to 20. The filtrate was then slowly neutralized with acetic acid.

acting (1) a compound having the formula 5 The lumazine, 3-sec-butyl product, which had separated as a light yellow precipitate, was separated from the 0 mother liquor by filtration, using a Biichner funnel. The ll, filtrate was set aside overnight, then salted with KCl,

L-NlIz and a second crop of precipitate was recovered. The comii bined final product was washed with tap water and dried H in a circulating air oven in which the air was maintained 0 at a temperature within the range of 80 to 100. The total recovery of dried product amounted to 8.4 g., or 71 wherein R is a member of the group consisting of alkyl percent of theory. It was determined by nuclear magnetic groups having from 2 to 8 carbon atoms, and cycloalkyl resonance analysis that the product (M.P. 179-182) groups having from 3 to 12 carbon atoms, with (2) sodiwas lumazine, 3-sec-butyl. urn hypochlorite, the reaction being carried out in the Elemental analysis gave the following results. Theory presence of sodium hydroxide and a suitable solvent, (percent): C, 54.5; H, 5.4; N, 25.4. Found (percent): preferably at elevated temperatures. C, 54.3; H, 5.5; N, 25.6.

The reaction is illustrated generally below, R having the EXAMPLE 3 meaning assigned in explamlng the immediately precedi f 1 Preparation of lumazlne, 3-cyclohexyl A flask equipped with a stirrer and a thermometer,

H and surrounded by a heating mantle was charged with H 240 ml. water, 3.1 g. sodium hydroxide and 70 ml. aque- Nm alga? /N i ous solution containing 5.2 g. NaOCl. Stirring was commenced, and was continued throughout the reaction.

\ 1 3 4 When this charging was complete, the temperature of the N ff (2)H+ N F 39 charge was 23; then 18.1 g. N-cyclohexyl-2,3-pyrazine- 0 (i dicarboxamide was added to the NaOCl-NaOH solution in the flask. After the pyrazinedicarboxamide dissolved,

The reaction is self-generating and will proceed in the the h p 0f the reaction mixture Was the absence of heat, but the reaction will go faster if the r l'eactlhh mixture Was then hfiated for total of abhut reaction mixture is heated. For that reason it is prefer- 36 mihules- Tht3 temperature after 6 mlhlltes 0f hfiatlhg able to heat the reaction mixture to a temperature from was after 2 mi and after -6 minutes about 50 to the boiling temperature thereof, most de- The heating mantle Was then removed, and the flask was i bl about 04m: d ld i as h temperature immersed in an ice bath and cooled to 18. The reaction for about /2 hour. Thereafter the mixture is cooled to 40 IniXtufQ Was then acidified, by making a gradual add t on room temperature and neutralized with acid at which time of glaclfal f acld, to 3 P of The rate of addltlon the reaction product precipitates. of acetic acid was controlled so that the tem per ature of This invention can be more Clearly underswuu by rah the reaction mixture 1n the flask dld HOlZ I'ISB significantly. Hence to the following examples The examples, The lumazme, 3- cyclohexyl product, which had separated ever are notintended tobe limiting as a wh1te prec p1tate, was separated from the mother lrquor by filtration, using a Biichner funnel. The final EXAMPLE 2 product was washed with tap water and dried in a circu- Preparation of lumazine 3 Sec buty1 lating air oven in which the air was maintained at a temperature within the range of 80 to 100.

A flask q pp h a stlrrer and a thermometfir, The total recovery of dry product, melting point 238- and Surrounded y a hgatmg mantle Was charged Wlth 240, amounted to 19.3 g. The product was subjected to 220 1111- Water, Sodlum hydroxlde P aque elemental analysis with the following results. Theory ous solution containing 4.7 g. NaOCl. Stirring was com- (percent); C 5 5; H, 5 N, 7 pound (percent); menced, and was continued throughout the reaction. c 5 H 5 ;r

When this charging was complete, the temperature of the charge was 22.5"; then, 12 g. N-sec-butyl 2,3 pyrazine- EXAMPLES 4 THROUGH 6 dicarboxamide was added to the NaOCl-NaOI-I solution Several other compounds of the invention have been in the flask. After the pyrazinedicarboxamide dissolved, produced by the above described method. Information the temperature of the reaction mixture was 25.5 the concerning starting materials, batch sizes, final product reaction mixture was then heated for a total of about 38 60 and yield for representative ones of such preparations is minutes. The temperature after 7 minutes of heating presented in Table I, below:

TABLE I Metal hypohalite Final product Starting amide Solu- Base Added Name or tion, name or water, Yield Ex. Name Grams formula Grams ml. formula Grams 1111. Name (grams) 4 N-cyclooctyl-2,3-pyrazine- 24 NaOCl 6.5 83 NaOH 7.1 400 Lumazino,3-cyclooeytyl. 22.1

dicarboxamide. 5 N-isopropy1-2,3-pyrazine- 25 NaOCl 8.9 111.6 NaOH 4.9 400 Lumazine, 3-isopropy1..- 20.7

dicarboxamide. 6 N-butyl-2,3-pyrazlne- 12 NaOCl 4.7 59 NaOH 2.6 220 Lumaziuo,3-n-butyl. 9.7

dicarboxamide.

Time-temperature readings for each of the reactions represented by the examples set forth in Table I are presented in Table II below. Zero time is when the amide is added to the reaction mixture.

The structure of the final compounds of Examples 4, and 6 were confirmed by elemental analysis, infrared and nuclear magnetic resonance spectra.

The other 3-substituted lumazines of this invention can be made by the procedures described in Examples 2 and 3, above, substituting the appropriate N-substituted-pyrazine-dicarboxamide for the N-sec-butyl-Z,3-pyrazinedicarboxamide and the -N-cyclohexyl pyrazinedicarboxamide starting materials.

Discussion of the reactants The best yields are obtained when one equivalent of base and one equivalent of hypohalite are used for each mole of the pyrazine dicarboxamide. Satisfactory results, however, have been achieved when as much as two equivalents of the hypohalite were used per mole of the pyrazinedicarboxamide.

While the method above described contemplates the use of alkali and alkaline earth metal hydroxides and alkali and alkaline earth metal hypohalites, sodium hydroxide and sodium hypohalite are preferred for economic reasons only. The other metal hydroxides and metal hypohalites are perfectly satisfactory but the cost thereof is much greater.

The metal hypohalite may be prepared by reacting chlorine or bromine with a water solution of an alkali metal or alkaline earth metal hydroxide, preferably sodium hydroxide. For example, a 1 N sodium hypochlorite solution can be prepared to reacting 79.98 g. NaOH with 70.90 g. chlorine (C1 in sufficient water to make one liter. It can be appreciated that one equivalent of bromine (Br can be substituted for chlorine to produce a sodium hypobromite solution; and in the same manner, 1 equivalent of an alkali or alkaline earth metal hydroxide can be substituted for the sodium hydroxide to produce a different metal hypohalite.

Water is the preferred solvent medium for the reaction due to low cost. Other solvents could be used alone or mixed with water such as alcohols or equivalents if they not not interfere with the course of the reaction. There is no advantage to this, however. The exact amount of water to be used is not critical. The best results have been achieved with approximately 2 l. of water per mole of the starting amide. Satisfactory results have been achieved with as much as 20 l. and as little as 1 l. of water.

Discussion of the reaction method In carrying out the process of producing the compositions of the invention the metal hypohalite should first be admixed with the base, and then the amide should be added thereto. If the components are not admixed in this manner, there is a tendency for the amide to hydrolyze to the corresponding acid resulting in a lower yield.

The temperature at which the reaction is conducted can range from 0 to with 60-80" being the most preferred. The reaction mixture should be held at the desired temperature for about /2 hour or until a negative test for hypohalite indicates the completion of the reaction.

At the end of the reaction, the reaction mixture is cooled to room temperature and neutralized with acid to a pH in the range of 10 to 4 to precipitate the product which can then be collected by filtration, washed and dried. The preferred pH range is from 5 to 6. A variety of acids can be used for the pH adjustments, but mineral acids and simple organic acids such as acetic acid are most preferred for economic reasons.

The 3-substituted lumazine compounds have been found to display unexpectedly high levels of herbicidal activity and to :be useful in controlling undesirable plants of both the monocotyledonous and the dicotyledonous species on either a postemergence or a preemergence basis.

By preemergence is meant that the compound is applied to the soil prior to emergence of the weed species sought to be controlled. This term, as used herein, also means the application of the herbicidal compounds falling within the scope of this disclosure to areas wherein useful or desirable plants are either growing or have been sown, but where the undesirable plants sought to be controlled have not as yet emerged.

By the term postemergence is meant that the compound is applied to the plant sought to be controlled after it has emerged from the soil surface. This term is also used to describe the application of herbicidally active compounds to soil surface in and around growing plants sought to be controlled by purposes of effecting root absorption by the undesirable plant species.

Especially active are the compounds where the 3-substituent is isopropyl, sec-butyl, cyclohexyl, or cyclooctyl.

The invention will be more clearly understood by r erence to the following examples.

EXAMPLE 7 The preemergence and postemergence herbicidal activity of lumazine, 3-cyclooctyl is shown in Table III be-. low.

In using the compound, seeds of the type of plants set forth in Table III Were sown in fresh soil. In the preemergence test the soil was sprayed with a solution of the test compound immediately after the seeds were planted, and before any noticable growth developed in the test area. The solution was about a 2 percent by weight solution of the compound in acetone and/ or alcohol. The compound was applied at the rate of 16 pounds per acre of soil surface.

Approximately three weeks after spray application, the herbicidal activity of the compound was determined by visual observation of the treated area in comparison with untreated control areas. These observations are reported below in Table III wherein the average activity rating is reported as the percent control of plant growth.

In the postemergence test the soil and developing plants were sprayed about two weeks after the seeds were sown. The compound was applied at the rate of 8 pounds per acre from about a 2 percent by weight solution of the test compound in alcohol and/or acetone. The postemergence herbicidal activity was measured in the same way as the preemergence activity; i.e., visual observation approximately 11 days after spraying, and expressed as the percent control of plant growth.

TABLE III [Compound applied: lumazine, 3-cyclooctyl] Pre- Post emergence emergence treatment treatment percent percent control control Alfalfa 100 10 Corn 30 10 Wild Oats- 100 10 Clicatgrass 100 Foxtail 40 50 Barnyardgrass.. 70 90 Crabgrass 90 100 Nutgrass. 30 J ohnsongras 90 100 Curled Dock- 100 100 Snapbeans. 100 100 Yellow Rocket 100 100 Chickweed. 100 100 Cueumber 100 100 Pigweed 100 Velvotle 100 100 Lambsquarters 100 10 1 N 0 value obtained.

The same solutions of the same compound can also be sprayed, for example along railroad right-of-ways, at an application rate of about 10 to 16 pounds per acre as a total herbicide, i.e., to prevent all vegetation. The other compounds disclosed herein can be used as preemergence or postemergence herbicides in a similar manner. In the case of lumazine, 3-cyclohexyl and lumazine, 3-sec-butyl, substantially the same application rates, e.g., as similar EXAMPLE 9 A solution of mg. of lumazine, 3-cyclooctyl in 5 cc. of acetone was added to water in a container, in an amount to give a concentration equivalent to 10 ppm. To the water were added growing floating aquatic weeds of the species Lemna minor and Salvinia braziliensis. Water was subsequently added to the container to compensate for evaporation as in Example 8. Two weeks after application of the chemical to the water, visual observation showed complete or 100 percent control of the Salvinia species and 50 percent control of Lemna minor.

It will be appreciated from the foregoing data and discussion that the 3-substituted lumazine family of compounds described herein has unexpected utility as herbicides, and that this unexpected utility prevails throughout the family. It will be noted that lumazines used in the method of this invention are substantially identical in structure to the S-Substituted pyridol[3,2-d]pyrimidines-2,4 (1H,3H)-diones shown and described in copending application Ser. No. 832,026 entitled Method of Controlling Plant Growth and 3-Substituted-Pyridol[3,2-d]Pyrimidine- 2,4(1H,3H)-Dione Compounds Used In Such Method, inventors Cooke, Compton, and Jacobs, filed June 10, 1969. The only difference between the compounds is that the base heterocyclic ring of the lumazines contains 2 nitrogen atoms rather than 1 as in the diones, as is shown in said application Ser. No. 832,026, such diones having the formula or salt solutions in water, are effective; this is also gen- H erally true of the other members of the lumazine family, 30 N 3 1 although slightly higher application rates may be required. 7 20:

Information concerning the 3-substituted lumazine 6 1 family of compounds applied as described, and discussed 5/ 6/ above as having an unexpectedly high order of herbicidal 8 activity, is presented in the following table.

TABLE IV.-COMPOUND APPLIED Lumazine, Lumazine, Lumaziue, Luniazlne- 3-isopropyl B-sec-butyl 3cyclohexyl 3-n-butyl (percent control) (percent control) (percent control) (percent control) Pro 1 Post 2 Pre Post Pre Post Pre Post 100 0 100 50 100 100 0 0 10 0 10 0 10 o 0 10 0 30 o 20 10 0 o 10 0 90 0 10 0 o 10 0 3c 0 20 1o 0 0 0 0 40 0 2e 1e 0 0 70 0 100 0 so 20 o 0 o o 40 0 100 100 c 0 7o 0 40 o 30 20 o 0 100 0 70 50 90 100 0 o 90 30 90 20 100 100 3c 10 100 100 100 100 100 0 7o 0 40 0 10c 90 90 o 100 10 10 60 100 100 100 o 100 20 100 90 0 0 100 0 100 90 100 100 o 0 Lambsquarters 100 40 100 100 100 100 0 7O Soybeans... r 0 0 Mari old r 0 100 1 Preemergence test=Compound applied at rate of 16 lb.lacre. 1 Postemergence tost=Compound applied at rate of 8 lb./acre.

The cycloalkyl substituted lumazines have additionally been found to possess high rates of herbicidal activity on aquatic weed species. This is demonstrated in the following examples.

EXAMPLE 8 showed complete or percent control of both species.

are highly active herbicides when R has been selected from the group consisting of alkyl groups having from 2 to 8 carbon atoms, or cycloalkyl groups having from 3 to 12 carbon atoms. A comparison between the herbicidal activity of the lumazines used in the method of this invention, and the diones referred to above will show that in all instances where the S-substituent is identical in both compounds the compounds are herbicidally effective. Thus, for example, lumazine, 3-cyclooctyl and 3'cyclooctyl pyrido [3,1-d]pyrimidine 2,4(1H),3H)-dione are both effective herbicides. Thus while the instant disclosure contains only a limited number of specific examples, the comparison between the lumazines and the diones relative to structure and herbicidal activity provides sufiicient basis for the limitations relative to the R substituent set forth herein because the limitations for the lumazines are the same as for the S-substituted pyrido[3,2-d] pyrimidine-2,4(1H,3H)-diones.

For practical use as herbicides, the compounds used in the method of this invention may be formulated with conventional agricultural carriers to obtain the desired concentration and to facilitate handling. For example, these compounds may be formulated into dusts by combining them with such materials as talc or clays. Wettable powder formulations may be obtained by adding a dispersing or suspending agent to the dust formulations referred to above.

If desired, the compounds may be applied as spray solutions which may be prepared by dissolving the compounds in suitable solvents, such as water, xylene, methylated naphthalenes, kerosenes, common agricultural oils, etc., in accordance with the well established agricultural practices. The choice of solvent to be used will be dictated by the solubility of the compound sought to be sprayed in that particular solvent system. Generally, it has been found that the majority of these compounds have a relatively low order of water solubility, so that the use of common agricultural organic solvents is the preferred practice.

The compounds used in the method of this invention may also be emulsified or suspended in water by adding wetting agents or emulsifying agents to aqueous systems containing one or more of the chemical compounds falling under this disclosure. These emulsified formulations are suitable for use in spraying directly upon the locus sought to be protected from undesirable vegetation. So far as has been determined no significant difference in effect is realized from the use of aqueous emulsified formulations or from organic solvent solutions of these herbicides, providing, of course, that a similar amount of chemical is employed in each instance of use.

If desired, the compounds can be converted to their salt forms, then dissolved in water and applied as water solutions. They can also be applied as addition compounds and the like.

The alkaline or alkaline earth metal and ammonium salts of the 3-substituted lumazines can be prepared by the reaction of the lumazine with the desired metal hydroxide or ammonium hydroxide.

Nitrogenous base addition compounds can be prepared by the addition of the desired nitrogenous base to a solution of the desired 3-substituted lumazine in a suitable inert organic solvent. The addition compound can then be isolated by standard procedures.

Suitable nitrogenous bases are substituted, unsubstituted, cyclic and acyclic amines and guanidines. The amines can be primary, secondary or tertiary amines, polyamines, arylamines, or heterocyclic amines.

Phenolic complexes are formed readily by co-melting the 3-substituted lumazine and phenol in a 1:1 to 2:1, lumazine: phenol mole ratio. They can also be formed by co-dissolving the reactants, in the same ratio in a nonpolar solvent such as nitromethane or a mixture of nitromethane and cyclohexane.

Acid addition compounds can be prepared by mixing a 3-substituted lumazine with an appropriate acid, at room temperature, in a liquid aromatic hydrocarbon solvent. The reaction is immediate. Generally any aromatic hydrocarbon can be used, but it is preferred that it be liquid between 20 and 30. Benzene, toluene and xylene are examples of satisfactory solvents.

The acid addition compounds can be precipitated with an excess of non-solvent liquid paraffin such as pentane, hexane, heptane or petroleum ether. The product precipitates as a solid or a viscous oil which can be sepa- 10 rated by filtration or vacuum evaporation. Alternatively, the product can be separated by vacuum evaporation of the reaction medium at low temperatures, preferably below 50. Precipitation with a non-solvent is the usual method.

Most acids having an ionization constant greater than 2 10 will form 3-substituted lumazine addition compounds. Preferred acids are halogenated aliphatic acids containing from 2 to 5 carbon atoms, halogenated benzoic acid, halogenated phenylacetic acids, halogenated phenoxy acetic acids, organic sulfonic acids, organic phosphonic acids and inorganic phosphoric acids. These acids are preferred because the lumazine addition compounds formed from them are highly phytotoxic and show good oil solubility.

The herbicidal activity of the acid addition compounds, complexes and the like is substantially the same as the herbicidal activity of the free 3-substituted lumazine when applied at the same active ingredient rate.

From the foregoing results it is apparent that the compounds falling within the scope of this invention possess unexpected herbicidal properties. Moreover, it has been shown that these compounds display a high rate of herbicidal activity while simultaneously demonstrating selectivity with respect to desirable, economic crops.

So far as concerns the amount of herbicide to be used this, of course, is subject to such considerations as the type of treatment to be made, the area to be treated, the type of weed sought to be controlled and the stage of development of the species being treated as well as the particular herbicide selected. Generally, however, concentrated herbicidal compositions of the present invention are prepared :so as to contain from 5 to about 6 0 percent of the active herbicidal component. Compositions which are suitable for as is application generally contain from 0.1 percent to about 10 percent of active herbicidal component.

Where it is desired to effect substantially complete elimination of all vegetation through use of one or more of the compounds falling within the scope of this invention, it is then necessary to apply a higher rate of the chemical agent to the soil, for example a rate of from 10 to 16 lbs/acre thereof, so as to obtain substantially complete soil sterilization.

What I claim is:

1. A compound of the formula wherein R is a member of the group consisting of alkyl groups having from 2 to 8 carbon atoms, and cycloalkyl groups having from 3 to 12 carbon atoms.

2. The compound of claim 1 wherein R is isopropyl. 3. The compound of claim 1 wherein R is sec-butyl. 4. The compound of claim 1 wherein R is cyclohexyl. 5. The compound of claim 1 wherein R is cyclooctyl.

References Cited Pfleiderer: CA. 52, 18457h (1958).

ALEX MAZEL, Primary Examiner R. V. RUSH, Assistant Examiner US. Cl. X.R. 

